tbuckley/cabot-search huggingface dataset:
School Performance in Third Grade After a Full-Day vs Part-Day Preschool Program
Authors: Arthur J. Reynolds, Nicole E. Smerillo, Suh-Ruu Ou, Marley Loveman-Brown, Nishank Varshney
Journal: JAMA (2023)

This study assesses whether learning gains associated with full-day preschool were sustained through third grade by analyzing achievement scores and need for remediation.
BRWD1 orchestrates small pre-B cell chromatin topology by converting static to dynamic cohesin
Authors: Malay Mandal, Mark Maienschein-Cline, Yeguang Hu, Azam Mohsin, Margaret L. Veselits, Nathaniel E. Wright, Michael K. Okoreeh, Young me Yoon, Jacob Veselits, Katia Georgopoulos, Marcus R. Clark
Journal: Nature Immunology (2023)
Risk of Bleeding Following Non–Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase
Authors: Tou-Yuan Tsai, Yu-Chang Liu, Wan-Ting Huang, Yu-Kang Tu, Shang-Quan Qiu, Sameer Noor, Yong-Chen Huang, Eric H. Chou, Edward Chia-Cheng Lai, Huei-Kai Huang
Journal: JAMA Internal Medicine (2023)

Importance Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non–vitamin K antagonist oral anticoagulants (NOACs). Objective To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs. Design, Setting, and Participants This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan’s National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO. Exposures NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment. Main Outcomes and Measures The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model. Results Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, −4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, −2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, −4.95% [95% CI, −10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score–matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis. Conclusions and Relevance In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.
Exploiting Iron Metabolism as a Therapeutic Vulnerability in Glioblastoma
Authors: Ali Nabavizadeh, Stephen J. Bagley
Journal: Clinical Cancer Research (2023)

Summary In this CCR Translations, we discuss pharmacologic ascorbate as a novel therapeutic for glioblastoma (GBM). Aberrant iron metabolism in GBM can be assessed noninvasively by MRI and exploited to potentially improve the efficacy of chemoradiotherapy. We contextualize the study's results and discuss the next steps to further develop this paradigm. See related article by Petronek et al., p. 283
Corrections to a Meta-Analysis of Oseltamivir Use in Preventing Hospitalization for Influenza
Authors: Todd C. Lee
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Cancer Screening Disparities Before and After the COVID-19 Pandemic
Authors: Aisha K. Lofters, Fangyun Wu, Eliot Frymire, Tara Kiran, Mandana Vahabi, Michael E. Green, Richard H. Glazier
Journal: JAMA Network Open (2023)

Breast, cervical, and colorectal cancer-screening disparities existed prior to the COVID-19 pandemic, and it is unclear whether those have changed since the pandemic.
Therapeutic Benefit From New Drugs From Pharmaceutical Companies
Authors: Joel Lexchin
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Machine culture
Authors: Levin Brinkmann, Fabian Baumann, Jean-François Bonnefon, Maxime Derex, Thomas F. Müller, Anne-Marie Nussberger, Agnieszka Czaplicka, Alberto Acerbi, Thomas L. Griffiths, Joseph Henrich, Joel Z. Leibo, Richard McElreath, Pierre-Yves Oudeyer, Jonathan Stray, Iyad Rahwan
Journal: Nature Human Behaviour (2023)
Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus
Authors: Jimin Lee, Samantha K. Zepeda, Young-Jun Park, Ashley L. Taylor, Joel Quispe, Cameron Stewart, Elizabeth M. Leaf, Catherine Treichel, Davide Corti, Neil P. King, Tyler N. Starr, David Veesler
Journal: Cell Host & Microbe (2023)

Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.
<i>ESR1</i> F404 Mutations and Acquired Resistance to Fulvestrant in <i>ESR1</i>-Mutant Breast Cancer
Authors: Belinda Kingston, Alex Pearson, Maria Teresa Herrera-Abreu, Li-Xuan Sim, Rosalind J. Cutts, Heena Shah, Laura Moretti, Lucy S. Kilburn, Hannah Johnson, Iain R. Macpherson, Alistair Ring, Judith M. Bliss, Yingwei Hou, Weiyi Toy, John A. Katzenellenbogen, Sarat Chandarlapaty, Nicholas C. Turner
Journal: Cancer Discovery (2023)

Fulvestrant is used to treat patients with hormone receptor-positive advanced breast cancer, but acquired resistance is poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in patients with activating ESR1 mutations in circulating tumor DNA (ctDNA). Baseline ESR1 mutations Y537S are associated with poor outcomes and Y537C with good outcomes. Sequencing of baseline and EOT ctDNA samples (n = 69) revealed 3/69 (4%) patients acquired novel ESR1 F404 mutations (F404L, F404I, and F404V), in cis with activating mutations. In silico modeling revealed that ESR1 F404 contributes to fulvestrant binding to estrogen receptor-alpha (ERα) through a pi-stacking bond, with mutations disrupting this bond. In vitro analysis demonstrated that single F404L, E380Q, and D538G models were less sensitive to fulvestrant, whereas compound mutations D538G + F404L and E380Q + F404L were resistant. Several oral ERα degraders were active against compound mutant models. We have identified a resistance mechanism specific to fulvestrant that can be targeted by treatments in clinical development. Novel F404 ESR1 mutations may be acquired to cause overt resistance to fulvestrant when combined with preexisting activating ESR1 mutations. Novel combinations of mutations in the ER ligand binding domain may cause drug-specific resistance, emphasizing the potential of similar drug-specific mutations to impact the efficacy of oral ER degraders in development. This article is featured in Selected Articles from This Issue, p. 201.
Morphological diversity of cancer cells predicts prognosis across tumor types
Authors: Rasoul Sali, Yuming Jiang, Armin Attaranzadeh, Brittany Holmes, Ruijiang Li
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Intratumor heterogeneity drives disease progression and treatment resistance, which can lead to poor patient outcomes. Here, we present a computational approach for quantification of cancer cell diversity in routine hematoxylin-eosin–stained histopathology images. Methods We analyzed publicly available digitized whole-slide hematoxylin-eosin images for 2000 patients. Four tumor types were included: lung, head and neck, colon, and rectal cancers, representing major histology subtypes (adenocarcinomas and squamous cell carcinomas). We performed single-cell analysis on hematoxylin-eosin images and trained a deep convolutional autoencoder to automatically learn feature representations of individual cancer nuclei. We then computed features of intranuclear variability and internuclear diversity to quantify tumor heterogeneity. Finally, we used these features to build a machine-learning model to predict patient prognosis. Results A total of 68 million cancer cells were segmented and analyzed for nuclear image features. We discovered multiple morphological subtypes of cancer cells (range = 15-20) that co-exist within the same tumor, each with distinct phenotypic characteristics. Moreover, we showed that a higher morphological diversity is associated with chromosome instability and genomic aneuploidy. A machine-learning model based on morphological diversity demonstrated independent prognostic values across tumor types (hazard ratio range = 1.62-3.23, P &amp;lt; .035) in validation cohorts and further improved prognostication when combined with clinical risk factors. Conclusions Our study provides a practical approach for quantifying intratumor heterogeneity based on routine histopathology images. The cancer cell diversity score can be used to refine risk stratification and inform personalized treatment strategies.
Biomimetic hybrid nanovesicles improve infected diabetic wound via enhanced targeted delivery
Authors: Guoyong Jiang, Jiahe Guo, Chengqi Yan, Yingjie He, Jing Chen, Maojie Zhang, Kaituo Xiang, Xuejiao Xiang, Chi Zhang, Yufeng Wang, Shuoyuan Liu, Pengjuan Nie, Tao Jiang, Yu Kang, Cheng Wang, Xiang Xu, Xiaofan Yang, Zhenbing Chen
Journal: Journal of Controlled Release (2023)
Lipid-like gemcitabine diester-loaded liposomes for improved chemotherapy of pancreatic cancer
Authors: Xiaowei Wang, Hongwei Lu, Fang Luo, Dan Wang, Apeng Wang, Xuelei Wang, Wenkai Feng, Xiaobo Wang, Jiayi Su, Mingliang Liu, Guimin Xia
Journal: Journal of Controlled Release (2023)
Tumor microenvironment-responsive self-assembly of barium titanate nanoparticles with enhanced piezoelectric catalysis capabilities for efficient tumor therapy
Authors: Zhuo Xiang, Lingling Xu, Yizhu Shan, Xi Cui, Bojing Shi, Yuan Xi, Panxing Ren, Xuemei Zheng, Chaochao Zhao, Dan Luo, Zhou Li
Journal: Bioactive Materials (2023)

Catalytic therapy based on piezoelectric nanoparticles has become one of the effective strategies to eliminate tumors. However, it is still a challenge to improve the tumor delivery efficiency of piezoelectric nanoparticles, so that they can penetrate normal tissues while specifically aggregating at tumor sites and subsequently generating large amounts of reactive oxygen species (ROS) to achieve precise and efficient tumor clearance. In the present study, we successfully fabricated tumor microenvironment-responsive assembled barium titanate nanoparticles (tma-BTO NPs): in the neutral pH environment of normal tissues, tma-BTO NPs were monodisperse and possessed the ability to cross the intercellular space; whereas, the acidic environment of the tumor triggered the self-assembly of tma-BTO NPs to form submicron-scale aggregates, and deposited in the tumor microenvironment. The self-assembled tma-BTO NPs not only caused mechanical damage to tumor cells; more interestingly, they also exhibited enhanced piezoelectric catalytic efficiency and produced more ROS than monodisperse nanoparticles under ultrasonic excitation, attributed to the mutual extrusion of neighboring particles within the confined space of the assembly. tma-BTO NPs exhibited differential cytotoxicity against tumor cells and normal cells, and the stronger piezoelectric catalysis and mechanical damage induced by the assemblies resulted in significant apoptosis of mouse breast cancer cells (4T1); while there was little damage to mouse embryo osteoblast precursor cells (MC3T3-E1) under the same treatment conditions. Animal experiments confirmed that peritumoral injection of tma-BTO NPs combined with ultrasound therapy can effectively inhibit tumor progression non-invasively. The tumor microenvironment-responsive self-assembly strategy opens up new perspectives for future precise piezoelectric-catalyzed tumor therapy.
Combiner and HyperCombiner networks: Rules to combine multimodality MR images for prostate cancer localisation
Authors: Wen Yan, Bernard Chiu, Ziyi Shen, Qianye Yang, Tom Syer, Zhe Min, Shonit Punwani, Mark Emberton, David Atkinson, Dean C. Barratt, Yipeng Hu
Journal: Medical Image Analysis (2023)
Removal of innate immune barriers allows efficient transduction of quiescent human hematopoietic stem cells
Authors: Erika Valeri, Giulia Unali, Francesco Piras, Monah Abou-Alezz, Giulia Pais, Fabrizio Benedicenti, Maria Rosa Lidonnici, Ivan Cuccovillo, Ilaria Castiglioni, Sergio Arévalo, Giulio Spinozzi, Ivan Merelli, Rayk Behrendt, Adrian Oo, Baek Kim, Nathaniel R Landau, Giuliana Ferrari, Eugenio Montini, Anna Kajaste-Rudnitski
Journal: Molecular Therapy (2023)

Quiescent human hematopoietic stem cells (HSC) are ideal targets for gene therapy applications due to their preserved stemness and repopulation capacities; however, they have not been exploited extensively because of their resistance to genetic manipulation. We report here the development of a lentiviral transduction protocol that overcomes this resistance in long-term repopulating quiescent HSC, allowing their efficient genetic manipulation. Mechanistically, lentiviral vector transduction of quiescent HSC was found to be restricted at the level of vector entry and by limited pyrimidine pools. These restrictions were overcome by the combined addition of cyclosporin H (CsH) and deoxynucleosides (dNs) during lentiviral vector transduction. Clinically relevant transduction levels were paired with higher polyclonal engraftment of long-term repopulating HSC as compared with standard ex vivo cultured controls. These findings identify the cell-intrinsic barriers that restrict the transduction of quiescent HSC and provide a means to overcome them, paving the way for the genetic engineering of unstimulated HSC.
The role of minimally invasive surgery within a multidisciplinary approach for patients with metastatic spine disease over a decade: A systematic review
Authors: Alexander J Schupper, Shrey Patel, Jeremy M Steinberger, Isabelle M Germano
Journal: Neuro-Oncology (2023)

Abstract Background Metastatic spine disease (MSD) occurs commonly in cancer patients causing pain, spinal instability, devastating neurological compromise, and decreased quality of life. Oncological patients are often medically complex and frail, precluding them form invasive procedures. To address this issue, minimally invasive spinal surgery (MISS) techniques are desirable. The aim of this study is to review published peer-reviewed literature and ongoing clinical trials to provide current state of the art. Methods A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, assessing MISS in MSD patients for the period 2013–2023. Innovations under development were assessed by querying and reviewing data from currently enrolling U.S. registered clinical trials. Results From 3,696 articles, 50 studies on 3,196 patients focused on spinal oncology MISS. The most commonly reported techniques were vertebral augmentation (VA), percutaneous spinal instrumentation, and radiofrequency ablation (RFA). Surgical instrumentation/stabilization techniques were reported in 10/50 articles for a total of 410 patients. The majority of studies focused on pain as a primary outcome measure, with 28/50 studies reporting a significant improvement in pain following intervention. In the United States, 13 therapeutic trials are currently recruiting MSD patients. Their main focus includes radiosurgery, VA and/or RFA, and laser interstitial thermal therapy. Conclusions Due to their medical complexity and increased fragility, MSD patients may benefit from minimally invasive approaches. These strategies are effective at mitigating pain and preventing neurological deterioration, while providing other advantages including ease to start/resume systemic/radiotherapy treatment(s).
Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation
Authors: Axel Jensen, Frances Swift, Dorien de Vries, Robin M D Beck, Lukas F K Kuderna, Sascha Knauf, Idrissa S Chuma, Julius D Keyyu, Andrew C Kitchener, Kyle Farh, Jeffrey Rogers, Tomas Marques-Bonet, Kate M Detwiler, Christian Roos, Katerina Guschanski
Journal: Molecular Biology and Evolution (2023)

Abstract Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented in introgressing regions, in line with adaptive introgression, whereas genes involved in pigmentation and morphology may contribute to reproductive isolation. In line with reports from other systems that hybridization might facilitate diversification, we find that some of the most species-rich guenon clades are of admixed origin. This study provides important insights into the prevalence, role, and outcomes of ancestral hybridization in a large mammalian radiation.
Reply
Authors: Lars Alfredsson, Lars Klareskog, Anna Karin Hedström
Journal: Arthritis & Rheumatology (2023)

Xu and Li assert a consistent dose-dependent associa�on between alcohol consump�on and the severity of RA by ci�ng a study inves�ga�ng the impact of body mass index and alcohol consump�on in Sco�sh workers, with liver disease morbidity and mortality as the outcomes (2).We contend that this study may not be par�cularly per�nent when evalua�ng the impact of alcohol consump�on in pa�ents with RA, par�cularly since RA is not men�oned within the study.Xu and Li make the claim that alcohol consump�on heightens the risk of flare-ups, referencing a review ar�cle on the effects of alcohol intake in autoimmune diseases (3).However, we could not locate any informa�on within this review that substan�ates the authors' asser�on.On the contrary, this review's findings suggest that low-to-moderate alcohol consump�on appears to confer protec�ve effects in terms of disease severity across various autoimmune condi�ons, including RA.We agree with Xu and Li that excessive alcohol consump�on will have nega�ve health effects, which we also clearly state in our ar�cle.Our objec�ve was to inves�gate the influence of alcohol consump�on on one-year follow-up outcomes specific to RA in newly diagnosed cases.In our sensi�vity analysis, where we excluded non-drinkers and, instead, compared those with low alcohol consump�on to those with moderate or high consump�on, the later groups showed lower hazards ra�os for adverse outcomes.Consequently, we do not believe that selec�ng non-drinkers as the reference group in our main analysis has significantly introduced bias.Finally, we wish to underscore two main messages from or ar�cle.First, we emphasize the need of conduc�ng in-depth research into the mechanisms that enable low to moderate alcohol consump�on to reduce inflamma�on and immunity, as previous mechanis�c studies have suggested (4).Second, we emphasize the importance of personalized communica�on with pa�ents regarding scien�fic data, recognizing both poten�al adverse and poten�al favorable effects of lifestyle choices.